HRP940577A2 - Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy - Google Patents
Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy Download PDFInfo
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- HRP940577A2 HRP940577A2 HR940577A HRP940577A HRP940577A2 HR P940577 A2 HRP940577 A2 HR P940577A2 HR 940577 A HR940577 A HR 940577A HR P940577 A HRP940577 A HR P940577A HR P940577 A2 HRP940577 A2 HR P940577A2
- Authority
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- Croatia
- Prior art keywords
- hydrogen
- thia
- halogen
- diazabicyclo
- octane
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 8
- 238000002560 therapeutic procedure Methods 0.000 title claims description 4
- 230000000259 anti-tumor effect Effects 0.000 title claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005544 phthalimido group Chemical group 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000001629 suppression Effects 0.000 abstract description 4
- 208000019065 cervical carcinoma Diseases 0.000 abstract description 2
- 239000000126 substance Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Description
Oblast tehnike kojoj izum pripada The technical field to which the invention belongs
Internacionalna klasifikacija C07D513/04 International classification C07D513/04
U našem prethodnom izumu EP 0 598 375 A2 od 25.05.1994. opisani su 5-tia-1,4-diazabiciklo[4.2.0]oktan-3,8-diokso spojevi opće formule I, In our previous invention EP 0 598 375 A2 dated 25.05.1994. 5-thia-1,4-diazabicyclo[4.2.0]octane-3,8-dioxo compounds of general formula I are described,
[image] [image]
gdje radikali imaju značenje: where the radicals have the meaning:
R1 je vodik, halogen; R 1 is hydrogen, halogen;
R2 je vodik, halogen , amino, PhCH2CONH, PhOCH2CONH, ftalimido, o-MeNHCOC6H4CONH, R2 is hydrogen, halogen, amino, PhCH2CONH, PhOCH2CONH, phthalimido, o-MeNHCOC6H4CONH,
3-o-klorfenil-5-metil-izoksazolil-4-karbonilamino; 3-o-chlorophenyl-5-methyl-isoxazolyl-4-carbonylamino;
R3 je vodik, alkil, benzil, heterocikl npr. izoksazol, pirazol; R 3 is hydrogen, alkyl, benzyl, heterocycle eg isoxazole, pyrazole;
n je 1 ili 2, n is 1 or 2,
te naznačena njihova korisnost kao aktivnih komponenata u lijekovima za antibakterijsku terapiju. and indicated their usefulness as active components in drugs for antibacterial therapy.
Predmet ovog izuma odnosi se također na spojeve opće formule I, odnosno njihovu upotrebu kao aktivnih komponenata koje se u određenim količinama ugrađuju u farmaceutske preparate djelotvorne za supresiju tumorskih stanica. The subject of this invention also relates to compounds of the general formula I, i.e. their use as active components that are incorporated in certain quantities into pharmaceutical preparations effective for suppressing tumor cells.
Prema našem poznavanju stanja tehnike nije poznato da se spojevi sličnih struktura kao ni drugih β-laktamskih struktura upotrebljavaju u antitumorskoj terapiji. According to our knowledge of the state of the art, it is not known that compounds with similar structures or other β-lactam structures are used in antitumor therapy.
Sada je pronađeno da 5-tia-1,4-diazabiciklo(4.2.0)oktan-3,8-diokso analogoni opće formule I, gdje radikali imaju značenje kako je prethodno navedeno, snažno potiskuju rast stanica karcinoma grla maternice (HeLa). Aplikacijom supstancija I u koncentracijama od 10-3 do 10-6 M pronađen je nakon 72 sata učinak supresije tumorskih stanica od 25% do 65%. Najbolji učinci postignuti su pri koncentraciji od 5x10-4M. It has now been found that 5-thia-1,4-diazabicyclo(4.2.0)octane-3,8-dioxo analogs of the general formula I, wherein the radicals are as defined above, potently suppress the growth of cervical carcinoma (HeLa) cells. Application of substances I in concentrations of 10-3 to 10-6 M resulted in tumor cell suppression of 25% to 65% after 72 hours. The best effects were achieved at a concentration of 5x10-4M.
Niže navedeni primjeri supresivnog učinka supstancija opće formule I kod karcinoma grla maternice, ukazuju i na moguću djelotvornost ovih spojeva i za supresiju drugih tumorskih stanica. The following examples of the suppressive effect of substances of the general formula I in cervical cancer indicate the possible effectiveness of these compounds for the suppression of other tumor cells.
Postupak testiranja Testing procedure
Stanice se uzgoje u vremenu od 12 sati u hranjivom mediju DMEM-a (Dulbeccov modificirani Eagleov medij) uz dodatak 10% seruma teleta (FCS), 2mM glutamina, 100 U/ml penicilina, 100 μg/ml streptomicina i lmM Herpes pH 7.4 kod temperature od 37°C uz protok smjese zraka i 5% CO2. Stanice se nasade u koncentraciji od 104 st./ml u pločice s 24 ili 96 bunarića, te se nakon 12 sati dodaju otopine supstancija I u koncentracijama 10-3 do 10-6 M. Sve su supstancije najprije priređene kao 10-1 M otopine u dimetilformamidu, a razrjeđivanjem s medijem za uzgoj stanica dobivene su željene koncentracije. Brojanjem stanica elektronskim brojačem 72 sata nakon dodavanja aktivne supstancije utvrđeni su supresivni učinci supstancija I kako je navedeno u primjerima: The cells are grown for 12 hours in DMEM nutrient medium (Dulbecco's modified Eagle's medium) with the addition of 10% calf serum (FCS), 2mM glutamine, 100 U/ml penicillin, 100 μg/ml streptomycin and 1mM Herpes pH 7.4 at temperature of 37°C with a flow of air mixture and 5% CO2. Cells are seeded at a concentration of 104 st./ml in plates with 24 or 96 wells, and after 12 hours, solutions of substances I are added in concentrations of 10-3 to 10-6 M. All substances were first prepared as 10-1 M solutions in dimethylformamide, and the desired concentrations were obtained by diluting with cell culture medium. By counting cells with an electronic counter 72 hours after the addition of the active substance, the suppressive effects of substance I were determined as stated in the examples:
Spoj Koncentracija Supresija Compound Concentration Suppression
Primjer 1 Example 1
[image] [image]
Primjer 2 Example 2
[image] [image]
Primjer 3 Example 3
[image] [image]
Primjer 4 Example 4
[image] [image]
Primjer 5 Example 5
[image] [image]
Claims (1)
Priority Applications (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR940577A HRP940577B1 (en) | 1994-09-21 | 1994-09-21 | Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy |
| ES95114673T ES2115303T3 (en) | 1994-09-21 | 1995-09-18 | USE OF 5-TIA-1,4-DIAZABICICLO (4.2.0) OCTAN-3,8-DIOXO COMPOUNDS IN ANTITUMORAL THERAPY. |
| EP95114673A EP0705606B1 (en) | 1994-09-21 | 1995-09-18 | Use of 5-Thia-1,4-diazabicyclo [4.2.0] octane-3,8-dioxo compounds in antitumor therapy |
| DE69501810T DE69501810T2 (en) | 1994-09-21 | 1995-09-18 | Use of 5-thia-1,4-diazabicyclo [4.2.0] octane-3,8-dioxo compounds in anti-tumor therapy |
| AT95114673T ATE164069T1 (en) | 1994-09-21 | 1995-09-18 | USE OF 5-THIA-1,4-DIAZABICYCLO (4.2.0> OCTANE-3,8-DIOXO COMPOUNDS IN ANTITUMOR THERAPY |
| JP7241717A JPH08310954A (en) | 1994-09-21 | 1995-09-20 | Pharmaceutical composition |
| RU95116239A RU2136284C1 (en) | 1994-09-21 | 1995-09-20 | Use of 5-thia-1,4-diazabicyclo[4,2,0]octane-3,8-dioxoderivatives in antitumor therapy |
| CZ952447A CZ285621B6 (en) | 1994-09-21 | 1995-09-20 | The use of 5-thia-1,4-diazabicyclo[4,2,0]octane-3,8-dioxo derivatives for preparing medicaments intended for treating tumor diseases |
| CA002158678A CA2158678C (en) | 1994-09-21 | 1995-09-20 | Use of 5-thia-1, 4-diazabicyclo/4.2.0/octane-3,8-dioxo compounds in antitumor therapy |
| SI9500297A SI9500297A (en) | 1994-09-21 | 1995-09-21 | Use of 5-thia-1,4-diazabicyclo/4.2.0/octane-3,8-dioxo compounds in antitumor therapy |
| HU9502770A HU218287B (en) | 1994-09-21 | 1995-09-21 | Use of 5-thia-1,4-diazabicyclo[4.2.0]octane-3,8-dioxo compounds in antitumor therapy |
| SK1170-95A SK280815B6 (en) | 1994-09-21 | 1995-09-21 | Use of 5-thia-1,4-diazabicyclo[4.2.0]octane-3,8-dioxo compounds in antitumor therapy |
| BG100020A BG62237B1 (en) | 1994-09-21 | 1995-09-21 | The use of 5-thio-1,4-diazobicyclo-[4,2,0]-octan-3,8-dioxocompounds in antitumour therapy |
| CN95116888A CN1127115A (en) | 1994-09-21 | 1995-09-21 | Use of 5-thia-1,4-diazabicyclo/4.2.0/octane-3,8-dioxo compounds in antitumor therapy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HR940577A HRP940577B1 (en) | 1994-09-21 | 1994-09-21 | Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP940577A2 true HRP940577A2 (en) | 1997-04-30 |
| HRP940577B1 HRP940577B1 (en) | 1998-12-31 |
Family
ID=10946157
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR940577A HRP940577B1 (en) | 1994-09-21 | 1994-09-21 | Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0705606B1 (en) |
| JP (1) | JPH08310954A (en) |
| CN (1) | CN1127115A (en) |
| AT (1) | ATE164069T1 (en) |
| BG (1) | BG62237B1 (en) |
| CA (1) | CA2158678C (en) |
| CZ (1) | CZ285621B6 (en) |
| DE (1) | DE69501810T2 (en) |
| ES (1) | ES2115303T3 (en) |
| HR (1) | HRP940577B1 (en) |
| HU (1) | HU218287B (en) |
| RU (1) | RU2136284C1 (en) |
| SI (1) | SI9500297A (en) |
| SK (1) | SK280815B6 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101671336B (en) * | 2009-09-23 | 2013-11-13 | 辽宁利锋科技开发有限公司 | Aromatic heterocyclic pyridine derivatives and analogs and preparation method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5598188A (en) * | 1979-01-23 | 1980-07-25 | Mitsui Toatsu Chem Inc | Novel cephalosporin and its preparation |
| JPS57171994A (en) * | 1981-04-15 | 1982-10-22 | Asahi Chem Ind Co Ltd | Novel compound |
| HRP921292A2 (en) | 1992-11-17 | 1994-08-31 | Pliva Pharm & Chem Works | 5-thia-1,4-diazabicyclo (4.2.0.)octane -3,8-dioxo analogs of beta-lactams, the process for the preparation and use thereof |
-
1994
- 1994-09-21 HR HR940577A patent/HRP940577B1/en not_active IP Right Cessation
-
1995
- 1995-09-18 ES ES95114673T patent/ES2115303T3/en not_active Expired - Lifetime
- 1995-09-18 DE DE69501810T patent/DE69501810T2/en not_active Expired - Fee Related
- 1995-09-18 EP EP95114673A patent/EP0705606B1/en not_active Expired - Lifetime
- 1995-09-18 AT AT95114673T patent/ATE164069T1/en not_active IP Right Cessation
- 1995-09-20 CA CA002158678A patent/CA2158678C/en not_active Expired - Fee Related
- 1995-09-20 RU RU95116239A patent/RU2136284C1/en active
- 1995-09-20 CZ CZ952447A patent/CZ285621B6/en not_active IP Right Cessation
- 1995-09-20 JP JP7241717A patent/JPH08310954A/en active Pending
- 1995-09-21 BG BG100020A patent/BG62237B1/en unknown
- 1995-09-21 SI SI9500297A patent/SI9500297A/en unknown
- 1995-09-21 SK SK1170-95A patent/SK280815B6/en unknown
- 1995-09-21 HU HU9502770A patent/HU218287B/en not_active IP Right Cessation
- 1995-09-21 CN CN95116888A patent/CN1127115A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HUT74422A (en) | 1996-12-30 |
| EP0705606B1 (en) | 1998-03-18 |
| SK280815B6 (en) | 2000-08-14 |
| CZ285621B6 (en) | 1999-10-13 |
| BG62237B1 (en) | 1999-06-30 |
| HU9502770D0 (en) | 1995-11-28 |
| DE69501810T2 (en) | 1998-09-24 |
| SI9500297A (en) | 1996-04-30 |
| CN1127115A (en) | 1996-07-24 |
| DE69501810D1 (en) | 1998-04-23 |
| ATE164069T1 (en) | 1998-04-15 |
| ES2115303T3 (en) | 1998-06-16 |
| BG100020A (en) | 1996-04-30 |
| CA2158678C (en) | 2000-04-18 |
| CZ244795A3 (en) | 1996-04-17 |
| CA2158678A1 (en) | 1996-03-22 |
| RU2136284C1 (en) | 1999-09-10 |
| EP0705606A1 (en) | 1996-04-10 |
| JPH08310954A (en) | 1996-11-26 |
| HU218287B (en) | 2000-07-28 |
| SK117095A3 (en) | 1996-09-04 |
| HRP940577B1 (en) | 1998-12-31 |
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